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| Name | Class |
|---|---|
| University of Helsinki | OTHER |
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The study determines how a 6 months oral immunotherapy (OIT) program with hen's egg (HE) effects cellular and humoral immune responses in 50 children with HE allergy. Clinical data, transcriptomics and epigenetics are combined and analyzed by advanced system biology methods. This study will provide better understanding of the effects and mechanisms of OIT.
Oral immunotherapy (OIT) is a therapeutic approach, where gradually increasing doses of a specific food allergen are administered orally. OIT can desensitize up to 80% of children with persistent food allergy, and in a subset lead to sustained immune tolerance. The immunologic mechanisms induced by OIT are still poorly understood.
In this randomized cross-over study, 50 children with challenge-confirmed hen's egg (HE) allergy will be randomized (2:1) to receive either active HE OIT or continue on an avoidance diet for 6 months after which active OIT is started. The immunological changes induced by OIT will be compared to the patient's initial status and to that of the patients on an avoidance diet.
Serum antibody and humoral mediator analyses as well as gene expression of blood mononuclear cell (PBMC) by genome-wide microarray assays will be studied. PBMCs will be stimulated with HE allergens and innate immunity agonists, and the differences in the expression profiles of messenger-RNAs as well as microRNAs will be studied. Single-cell sequencing and sorting of regulator T cells (Tregs) will be performed focusing on their transcriptomic responses and gene methylation. Finally, clinical data, transcriptomics and epigenetic changes will be combined and analyzed by advanced system biology methods.
This study will provide better understanding of the effects and mechanisms of OIT and identify biomarkers for selection of patients benefitting from personalized OIT.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hen's egg OIT | Active Comparator | Daily intake of gradually increasing doses of egg white protein under a 32 weeks period, continued by regular, daily intake of 1000 mg egg white protein. |
|
| Hen's egg avoidance | No Intervention | Hen's egg is avoidance diet is continued. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hen's egg OIT | Dietary Supplement | Increasing doses of egg white protein administered orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| OIT-induced allergen-specific antibody responses | The amount of specific serum IgE, IgG4, and IgA antibodies (kU/L) to the major egg allergens (Gal d1 - d4) will be measured by ImmunoCAP after 0, 14, and 32 weeks of OIT or avoidance. | Up to 32 weeks |
| OIT-induced changes in the peripheral blood cell transcriptome | Gene expression of blood mononuclear cells (PBMC) after 0, 14 and 32 weeks of OIT or avoidance will be studied. Total-RNA extracted from PBMCs will be used for microarrays. The genome-wide expression of the approximately 25.000 genes will be investigated on Agilent SurePrint G3 Human Gene Expression v3 arrays. | Up to 32 weeks |
| OIT-induced allergen-specific expression profiles of messenger-RNAs and microRNAs | Comprehensive highthroughput sequencing for long (mRNA) and short (miRNA) coding gene expression approach will be used to investigate transcriptional changes in exposed blood cells after different stimulations (egg extract, LPS, PolyI:C) | Up to 32 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| The prorportion of participants able to consume 1000mg of egg protein after 32 weeks of OIT | Measured in mg of egg protein consumed without symptoms | Up to 32 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mika J Mäkelä, Professor | Skin and Allergy Hospital, Helsinki University Central Hospital | Study Director |
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| ID | Term |
|---|---|
| D005512 | Food Hypersensitivity |
| ID | Term |
|---|---|
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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Patients are randomized 2:1 to receive active HE OIT or continue on an elimination diet after which active HE OIT is started.
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